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This article discusses the evidence supporting the resection of glioblastoma beyond the borders of contrast-enhancing tumor. While several techniques for this have been described, including a so-called FLAIRectomy, lobectomy, or via the use of adjuncts such as fluorescence or intraoperative MRI, the optimal extent of additional resection has yet to be established. Many authors have noted a survival benefit with supramarginal resection without significant additional morbidity., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Meningiomas are the most common primary intracranial tumor. Recently, various genetic classification systems for meningioma have been described. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored., Methods: 88 tumor samples were analyzed in this study. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA)., Results: Fifty-seven patients had no history of smoking, twenty-two were past smokers, and nine were current smokers. The clinical data showed no major differences in natural history across smoking status. WES revealed absence of AKT1 mutation rate in current or past smokers compared to non-smokers (p = 0.046). Current smokers had increased mutation rate in NOTCH2 compared to past and never smokers (p < 0.05). Mutational signature from current and past smokers showed disrupted DNA mismatch repair (cosine-similarity = 0.759 and 0.783). DEG analysis revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = - 3.97, padj = 0.0347 and Log2FC = - 4.18, padj = 0.0304) and never smokers (Log2FC = - 3.86, padj = 0.0235 and Log2FC = - 4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR < 25% each)., Conclusion: In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Meningiomas are the most common primary intracranial tumor. Seizures are common sequelae of meningioma development. Meningioma patients with seizures can be effectively treated with resection, with reports of seizure freedom of 60%-90%. Still, many patients manifest persistent epilepsy. Determining factors associated with worsened seizure outcomes remains critical in improving the quality of life for these patients. The authors sought to identify clinical, radiological, and histological factors associated with worse seizure outcomes in patients with supratentorial meningioma and preoperative seizures., Methods: The authors retrospectively reviewed the charts of 384 patients who underwent meningioma resection from 2008 to 2020. The charts of patients with a documented history of preoperative seizures were further reviewed for clinical, radiological, operative, perioperative, histological, and postoperative factors associated with seizures. Engel class at last follow-up was retrospectively assigned by the authors and further grouped into favorable (class I) and worse (class II-IV) outcomes. Factors were subsequently compared by group using comparative statistics. Univariable and multivariable regression models were utilized to identify independent predictors of worse seizure outcome., Results: Fifty-nine patients (15.4%) were found to have preoperative seizures, of whom 57 had sufficient postoperative data to determine Engel class outcome. Forty-two patients (74%) had Engel class I outcomes. The median follow-up was 17 months. Distinct margins on preoperative imaging (p = 0.012), Simpson grade I resection (p = 0.004), postresection ischemia (p = 0.019), WHO grade (p = 0.019), and recurrent disease (p = 0.015) were found to be the strongest predictors of Engel class outcome in univariable logistic regression. MIB-1 index (p = 0.001) and residual volume (p = 0.014) at last follow-up were found to be the strongest predictors of Engel class outcome in univariable generalized linear regression. Postresection ischemia (p = 0.012), WHO grade (p = 0.022), recurrent disease (p = 0.038), and MIB-1 index (p = 0.002) were found to be the strongest independent predictors of Engel class outcomes in multivariable analysis., Conclusions: Postresection ischemia, higher WHO grade, elevated MIB-1 index, and disease recurrence independently predict postresection seizure persistence in patients with supratentorial meningioma. Further understanding of the etiology of these markers may aid in elucidation of this complex disease process and guide management to prevent worse outcomes.

Intrawound liposomal bupivacaine is a long-acting local anesthetic used to decrease postoperative pain in various procedures. Although it is used in posterior cervical and suboccipital approaches in the adult population, it is currently off-label for pediatrics. This quality improvement (QI) project examines intrawound liposomal bupivacaine for pediatric Chiari decompression and evaluates its role in postoperative opioid consumption., Methods: We retrospectively analyzed all patients 0-18 years old of age who underwent Chiari decompression from January 2017 to July 2019 at our tertiary care hospital. Demographic and clinical data regarding postoperative opioid use, subjective and objective pain control, length of stay, discharge medications, and comorbid conditions were collected., Results: We included 30 patients in this study: 19 females and 11 males. Of these, 6 received an intrawound injection of liposomal bupivacaine., Patients: treated with liposomal bupivacaine require fewer opioids while admitted. There was no apparent difference in pain control immediately postoperatively, pain control at clinical follow-up, or inpatient length of stay between each group. Patients who received liposomal bupivacaine did not require opioid analgesics at the time of discharge from the hospital., Conclusion: The use of intrawound liposomal bupivacaine may decrease inpatient and outpatient postoperative opioid consumption amongst pediatric patients following Chiari decompression while providing adequate pain control. We investigate liposomal bupivacaine perioperative blockade in this QI project as a viable option for opioid-sparing pain control in the postoperative setting for the pediatric population. Future investigation via clinical trials and more extensive prospective studies may glean further insights into efficacy., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Zinc uptake in bacteria is essential to maintain cellular homeostasis and survival. ZnuABC is an important zinc importer of numerous bacterial genera, which is expressed to restore zinc homeostasis when the cytosolic concentration decreases beyond a critical threshold. Upon zinc limitation the fast-growing nonpathogenic organism Mycobacterium smegmatis (MSMEG) as well as the ruminant pathogen M. avium subsp. paratuberculosis (MAP) increases expression of genes encoding ZnuABC homologues, but also of genes encoding other transporters. This suggests an involvement of these transporters in zinc homeostasis. Here we characterized the putative zinc transporters of MSMEG (ZnuABC and ZnuABC2) and MAP (ZnuABC, MptABC, and MAP3774-76). Deletion of either ZnuABC or ZnuABC2 in MSMEG did not lead to growth defects, but to an increased expression of zinc marker genes in MSMEGΔ znu ABC, indicating cytosolic zinc limitation. However, chromatin immunoprecipitation proved direct binding of the global zinc regulator Zur to promoter regions of both znu ABC and znu ABC2. Simultaneous deletion of both transporters caused severe growth defects, which could be restored either by homologous complementation with single ZnuABC transporters or supplementation of growth media with zinc but not iron, manganese, cobalt, or magnesium. Heterologous complementation of the double mutant with MAP transporters also resulted in reconstitution of growth. Nonradioactive FluoZin TM -3AM zinc uptake assays directly revealed the competence of all transporters to import zinc. Finally, structural and phylogenetic analyses provided evidence of a novel class of ZnuABC transporters represented by the ZnuABC2 of MSMEG, which is present only in actinobacteria, mainly in the genera Nocardia , Streptomyces and fast growing Mycobacteria IMPORTANCE Zinc is necessary for bacterial growth but simultaneously toxic when in excess. Hence, bacterial cells have developed systems to alter intracellular concentration. Regulation of these systems is primarily executed at transcriptional level by regulator proteins which sense femtomolar changes in the zinc level. In environmental and pathogenic mycobacteria zinc starvation induces expression of common zinc import systems such as the ZnuABC transporter, but also of other additional not yet characterized transport systems. In this study, we characterized the role of such systems in zinc transport. We showed that transport systems of both species whose transcription is induced upon zinc starvation can exchangeably restore cellular zinc homeostasis in transporter deficient mutants by transporting zinc into the cell., (Copyright © 2021 American Society for Microbiology.)

Here, we report the complete genome sequence of the Mycobacterium avium subsp. paratuberculosis reference strain DSM 44135, amended with a manual genome reannotation. The strain was originally described as M. paratuberculosis strain 6783. It was isolated from feces from a dairy cow in northern Germany., (Copyright © 2020 Goethe et al.)

Foraminal disc herniation presents with an operative challenge, as it often requires facetectomy, which can result in segmental instability. The intraforaminal approach includes partial pars resection and medial facetectomy and allows for direct visualization of the nerve roots and herniated disc in the foramen without violating the joint, with good clinical outcomes. Herein, we describe a retrospective series of patients that underwent minimally invasive paramedian approach with hemilaminectomy, partial medial pars resection, medial facetectomy for foraminal disc herniation. Demographics and clinical outcomes were obtained from medical records. Improvement in functional outcomes was evaluated using the pre and post-operative Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). A total of 23 patients were included in this study. The average age was 56.47 ± 9.4 yrs and body mass index was 31.92 ± 7.7 kg/m 2 . 47.8% of cases were L4-5 FDH. The estimated blood loss was 31.32 ± 19.8 ml. The average length of hospital stay was 1.11 ± 0.3 days. All patients were discharged home. Overall, there was a significant improvement in the VAS (pre-op: 8.21 ± 2.1; post-op: 2.59 ± 2.7; p-value: <0.0001) and ODI (pre-op: 57.16 ± 13.2; post-op: 21.47 ± 9.9; p-value: <0.0001). The minimally invasive paramedian approach provides satisfactory outcomes as a safe strategy in the treatment of foraminal disc herniation. Herein, there was a significant improvement in pain and functional outcomes, minimal blood loss and decreased hospital stay., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Zinc homeostasis is crucial for bacterial cells, since imbalances affect viability. However, in mycobacteria, knowledge of zinc metabolism is incomplete. Mycobacterium smegmatis (MSMEG) is an environmental, nonpathogenic Mycobacterium that is widely used as a model organism to study mycobacterial metabolism and pathogenicity. How MSMEG maintains zinc homeostasis is largely unknown. SmtB and Zur are important regulators of bacterial zinc metabolism. In mycobacteria, these regulators are encoded by an operon, whereas in other bacterial species, SmtB and Zur are encoded on separate loci. Here, we show that the smtB - zur operon is consistently present within the genus Mycobacterium but otherwise found only in Nocardia , Saccharothrix , and Corynebacterium diphtheriae By RNA deep sequencing, we determined the Zur and SmtB regulons of MSMEG and compared them with transcriptional responses after zinc starvation or excess. We found an exceptional genomic clustering of genes whose expression was strongly induced by zur deletion and zinc starvation. These genes encoded zinc importers such as ZnuABC and three additional putative zinc transporters, including the porin MspD, as well as alternative ribosomal proteins. In contrast, only a few genes were affected by deletion of smtB and zinc excess. The zinc exporter ZitA was most prominently regulated by SmtB. Moreover, transcriptional analyses in combination with promoter and chromatin immunoprecipitation assays revealed a special regulation of the smtB - zur operon itself: an apparently zinc-independent, constitutive expression of smtB - zur resulted from sensitive coregulation by both SmtB and Zur. Overall, our data revealed yet unknown peculiarities of mycobacterial zinc homeostasis. IMPORTANCE Zinc is crucial for many biological processes, as it is an essential cofactor of enzymes and a structural component of regulatory and DNA binding proteins. Hence, all living cells require zinc to maintain constant intracellular levels. However, in excess, zinc is toxic. Therefore, cellular zinc homeostasis needs to be tightly controlled. In bacteria, this is achieved by transcriptional regulators whose activity is mediated via zinc-dependent conformational changes promoting or preventing their binding to DNA. SmtB and Zur are important antagonistically acting bacterial regulators in mycobacteria. They sense changes in zinc concentrations in the femtomolar range and regulate transcription of genes for zinc acquisition, storage, and export. Here, we analyzed the role of SmtB and Zur in zinc homeostasis in Mycobacterium smegmatis Our results revealed novel insights into the transcriptional processes of zinc homeostasis in mycobacteria and their regulation., (Copyright © 2020 Goethe et al.)

Background: In the pediatric neurosurgical population, understanding how to mitigate the effects of disease on children's physical ability, social and psychological well-being, and education can have lasting effects on their development and family. Understanding parents' perceptions of their children's health-related quality of life (HRQoL) is crucial in proper counseling, management of expectations, establishment of a healthy patient/parent-physician relationship, and understanding the role and impact of health care. In this study we sought to examine the differences between patient and parent perceptions of HRQoL and the factors that influence these differences., Methods: A standardized survey (PedsQL Inventory) to assess physical, psychological, and social function and school performance was administered to both parents and patients in a general pediatric neurosurgery outpatient clinic from 2015-2018., Results: 197 encounters with 179 patients occurred in the study period. There were 105 male and 92 female patients across various ethnic backgrounds. The most common diagnoses were tumor (23.4%) and vascular malformation (16.2%). Parent overall scores were lower than their children's (72.5 vs. 76.4, P < 0.01). Parent scores of physical function (74.3 vs. 78.7, P < 0.01) and overall psychosocial function (71.5 vs. 75.3, P < 0.01) were also lower. Parent scores in all domains of the PedsQL were correlated with overall score difference (P < 0.01), but only child scores of overall psychosocial (P < 0.03) and school function (P < 0.04) were correlated with overall score difference., Conclusions: Parents have more negative assessments of their children's HRQoL compared with their children in all domains assessed by the PedsQL. Further research is needed to identify factors that contribute to these discrepancies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Object: While it has been extensively studied in adults, the role of spinal angiography in children with suspected spinal vascular malformations is not fully characterized. With special implications regarding technique, radiation dose, and pathology, we sought to review our single-center experience with pediatric spinal vascular pathology and use a systematic review of the literature to further identify its role in pediatrics., Methods: A retrospective chart review was conducted under IRB approval for all patients age 0-18 years old who underwent spinal angiography at our institution between 2007 and 2018 for concern for spinal vascular pathology. A simultaneous systematic review was conducted via dedicated search terms in two distinct databases and reviewed to identify all studies referring to spinal angiography or angiograms in pediatric patients., Results: Six patients were included. Three patients (50%) had vascular malformations confirmed on diagnostic angiography and underwent subsequent endovascular treatment. Two patients (33.3%), one with hematomyelia and one with spinal cord infarction, had negative diagnostic angiograms. One patient (16.7%) had a spinal tumor and underwent angiography for further evaluation preoperatively. Spinal angiography was used to aid in diagnosis, preoperative planning, and treatment in these cases. It was demonstrated to be safe in this patient population, with no untoward events, minimal radiation dose, and possible therapeutic applications in select cases. The systematic review identified 11 studies regarding pediatric spinal angiography. These ranged from single case reports to case series of up to 38 patients and highlighted the role of spinal angiography in diagnosis, endovascular treatment, preoperative planning, and postoperative follow-up., Conclusions: Spinal angiography may be used in a variety of scenarios to better understand the architecture of vascular spinal lesions and facilitate endovascular intervention. While its application in both adult and pediatric pathology is limited to select cases, spinal angiography remains a key diagnostic procedure when approaching vascular lesions or tumors of the spine, assessing for etiology of spinal cord infarcts, and in the evaluation of unexplained hemorrhage in the spinal canal.

Actinobacillus pleuropneumoniae is a capnophilic pathogen of the porcine respiratory tract lacking enzymes of the oxidative branch of the tricarboxylic acid (TCA) cycle. We previously claimed that A. pleuropneumoniae instead uses the reductive branch in order to generate energy and metabolites. Here, we show that bicarbonate and oxaloacetate supported anaerobic growth of A. pleuropneumoniae Isotope mass spectrometry revealed heterotrophic fixation of carbon from stable isotope-labeled bicarbonate by A. pleuropneumoniae , which was confirmed by nano-scale secondary ion mass spectrometry at a single-cell level. By gas chromatography-combustion-isotope ratio mass spectrometry we could further show that the labeled carbon atom is mainly incorporated into the amino acids aspartate and lysine, which are derived from the TCA metabolite oxaloacetate. We therefore suggest that carbon fixation occurs at the interface of glycolysis and the reductive branch of the TCA cycle. The heme precursor δ-aminolevulinic acid supported growth of A. pleuropneumoniae , similar to bicarbonate, implying that anaplerotic carbon fixation is needed for heme synthesis. However, deletion of potential carbon-fixing enzymes, including PEP-carboxylase (PEPC), PEP-carboxykinase (PEPCK), malic enzyme, and oxaloacetate decarboxylase, as well as various combinations thereof, did not affect carbon fixation. Interestingly, generation of a deletion mutant lacking all four enzymes was not possible, suggesting that carbon fixation in A. pleuropneumoniae is an essential metabolic pathway controlled by a redundant set of enzymes. A double deletion mutant lacking PEPC and PEPCK was not impaired in carbon fixation in vitro but showed reduction of virulence in a pig infection model., (Copyright © 2019 American Society for Microbiology.)

Acute myeloid leukemia (AML) and glioblastoma (GB) are two malignancies associated with high incidence of treatment refractoriness and generally, uniformly poor survival outcomes. While the former is a hematologic (i.e. a "liquid") malignancy and the latter a solid tumor, the two diseases share both clinical and biochemical characteristics. Both diseases exist predominantly in primary (de novo) forms, with only a small subset of each progressing from precursor disease states like the myelodysplastic syndromes or diffuse glioma. More importantly, the primary and secondary forms of each disease are characterized by common sets of mutations and gene expression abnormalities. The primary versions of AML and GB are characterized by aberrant RAS pathway, matrix metalloproteinase 9, and Bcl-2 expression, and their secondary counterparts share abnormalities in TP53, isocitrate dehydrogenase, ATRX, inhibitor of apoptosis proteins, and survivin that both influence the course of the diseases themselves and their progression from precursor disease. An understanding of these shared features is important, as it can be used to guide both the research about and treatment of each.